This invention relates to highly isomerically pure stereoisomers of glycidol derivatives, and more particularly to the preparation of highly purified diastereomers of glycidyl camphorsulfonate.
Stereoisomers of glycidol, having the formula (1) and certain of their derivatives are important intermediate compounds for asymmetric synthesis in various commercially important fields. They have been used to prepare pharmaceuticals such as antibacterial agents and .beta.-blockers, Other uses include the preparation of pheromones, useful phospholipids, and other biologically active substances. ##STR1##
Glycidol itself is relatively unstable and water soluble, rendering its preparation technically demanding. It is produced by a potentially hazardous peroxide oxidation process, and is a suspected carcinogen. It is commercially available in optical purity of 88-90%.
In U.S. Pat. No. 4,831,101 to Jellinek et al it is shown that polyglycidyl ethers can be prepared by reacting a member of the group consisting of mono- and polyvalent phenols, aromatic amines, and aromatic carboxylic acids with an epihalohydrin. U.S. Pat. No. 4,810,808 to Tomita et al discloses another process for preparing a polyglycidyl compound in which an aromatic hydroxycarboxylic acid having a phenolic hydroxyl group is reacted with an epihalohydrin in the presence of a phase transfer catalyst, followed by dehydrohalogenation.
In U.S. Pat. No. 4,931,576 to Wirth et al there is disclosed a process for producing a glycidyl thioether by reacting a mercaptan with epichlorohydrin.
U.S. Pat. No. 3,053,855 to Maerker et al discloses that glycidyl esters can be prepared by reacting epichlorohydrin with an aqueous solution of an alkali metal salt of an organic carboxylic acid in the presence of a quaternary ammonium halide.
The processes disclosed in the above noted patents are not directed to the production of optical isomers of the glycidyl derivatives.
The production of optical isomers of glycidol derivatives is known. Certain arenesulfonate derivatives of partially purified glycidol can be crystallized to higher optical purity, but only at significant losses of product. 2,3-Isopropylideneglyceraldehyde having the formula (2) can be obtained as pure optical isomer from D-mannitol or ascorbic acid by processes involving oxidation. However the oxidants, which include lead tetraacetate and sodium periodate, are expensive and environmentally unattractive. Also, 2,3-Isopropylideneglyceraldehyde is sensitive to acid or base-catalyzed racemization, and is difficult to store. It is not commercially available. ##STR2##
Another glycidol derivative, epichlorohydrin, having the formula (3) is obtainable commercially as either pure optical isomer. It may be produced by an enzymatic resolution process, but is quite expensive. ##STR3## Furthermore epichlorohydrin is volatile, highly toxic, and a suspected carcinogen.
Still another compound, benzyl glycidyl ether, having the formula (4), is commercially available as either optical isomer. The optical purity can be as low as 76%, and the compound also is rather expensive. ##STR4##
The preeminent preparative methodology currently used to prepare glycidol derivatives is either enzymatic resolution or Sharpless Asymmetric Epoxidation. As aforementioned, these methods present problems of incomplete optical purity, long, expensive, and hazardous synthesis routes, and handling and storage instabilities.